The halogenated ether, 1,1,2-trifluoro-2-chloroethyl difluoromethyl ether, CHF.sub.2 OCF.sub.2 CHFCl, is a valuable inhalant anesthetic, enflurane, made and sold under the trademark ETHRANE by Airco, Inc., Montvale, N.J. 07645. It is referred to hereafter as enflurane.
The presently-employed process for manufacturing this anesthetic material generates a number of by-product streams, each characterized by having more chlorine in the molecule than does the desired anesthetic product. One such by-product stream contains the compound of CF.sub.2 HOCF.sub.2 CFCl.sub.2, which is very difficult to remove from the desired product by distillation or other separating technique, and of course it represents a yield loss for the presently-employed process.
Other by-product streams are produced in the presently-employed process as "bottoms" from the vacuum stills. These bottoms contain the following components in varying proportions:
CH.sub.2 ClOCF.sub.2 CHFCl PA1 CCl.sub.3 OCF.sub.2 CHFCl PA1 CCl.sub.2 HOCF.sub.2 CHFCl PA1 CCl.sub.2 HOCF.sub.2 CFCl.sub.2 PA1 CClH.sub.2 OCF.sub.2 CFCl.sub.2 PA1 CCl.sub.3 OCF.sub.2 CFCl.sub.2 PA1 (a) CX.sub.3 OCY.sub.2 CZ.sub.3 PA1 CX.sub.3 is CF.sub.3, CH.sub.3, CH.sub.2 F, CF.sub.2 CL, CF.sub.2 Br, or CHF.sub.2 ; PA1 CZ.sub.3 CY.sub.2 is CF.sub.3 CCL.sub.2, CF.sub.3 CClBr, CF.sub.3 CBr.sub.2, CFCl.sub.2 CF.sub.2, CFCl.sub.2 CFCl, CFCl.sub.2 CFBr, CFBrClCF.sub.2, CFClBrCFCl, CFBrClCFBr, CCl.sub.3 CF.sub.2, CFBr.sub.2 CF.sub.2, CFBr.sub.2 CFCl, CFBr.sub.2 CFBr, CCl.sub.2 BrCF.sub.2, CClBr.sub.2 CF.sub.2 or CBr.sub.3 CF.sub.2 PA1 (b) CX.sub.3 CY.sub.2 OCY.sub.2 CX.sub.3 PA1 CF.sub.3 CCl.sub.2, CF.sub.3 CClBr, CF.sub.3 CBr.sub.2, CFCl.sub.2 CF.sub.2, CFCl.sub.2 CFCl, CFCl.sub.2 CFBr, CFBrClCF.sub.2, CFBrClCFCl, CFBrClCFBr, CCl.sub.3 CF.sub.2, CFBr.sub.2 CF.sub.2, CFBr.sub.2 CFCl, CFBr.sub.2 CFBr, CCl.sub.2 BrCF.sub.2, CClBr.sub.2 CF.sub.2 or CBr.sub.3 CF.sub.2 ; PA1 CF.sub.3 CH.sub.2, CF.sub.3 CHF, CF.sub.3 CHCl, CF.sub.3 CHBr, CF.sub.3 CF.sub.2, CF.sub.3 CFCl, CF.sub.3 CFBr, CH.sub.3 CH.sub.2, CHFCH.sub.2, CHF.sub.2 CF.sub.2, CFClCF.sub.2, CF.sub.2 ClCFCl, CF.sub.2 ClCFBr, CF.sub.2 BrCF.sub.2, CF.sub.2 BrCFCl, CF.sub.2 BrCFBr, CHFBrCF.sub.2, CHCl.sub.2 CF.sub.2, CHClBrCF.sub.2 or CHBr.sub.2 CF.sub.2.
At the present time, these materials are useless by-products that reduce the efficiency of the currently-employed process.
Another important halogenated ether anesthetic is 1-chloro-2-trifluoro difluoromethyl ether, CF.sub.3 CHClOCHF.sub.2, isoflurane, made and sold under the trademark FORANE by Airco, Inc. It is referred to hereafter as isoflurane. In the process for manufacturing this anesthetic, care must be exercised to avoid by-product formation, and the process now in use achieves low conversions to the desired product. Representative by-products produced include CF.sub.3 CCl.sub.2 OCHF.sub.2, which has been considered to be useless in the past.
The selective reduction of halogenated aliphatic ethers is extremely difficult to accomplish because of the different responses exhibited by ethers of this kind to a given reactant or to given reactants. Thus, there are three important reactions that halogenated aliphatic ethers may undergo in the presence of a base.
First, a hydrolysis or nucleophilic displacement reaction may occur. This is a reaction in which the halogen atom is replaced by OH, OR, or other nucleophilic group, as represented by the equation: EQU B+R--O--R'Cl.fwdarw.RO--R'--B+Cl
where B is OH or OR.
Second, dehydrohalogenation may occur. In this reaction, hydrogen and halogen are removed from adjacent carbon atoms to form a double bond: ##STR1## This type of reaction is described in U.S. Pat. No. 2,803,666, where this reaction occurs: ##STR2## It is also described by Corley et al. in 78 JACS 3489 at 3491 and 3492, as for example in this preparation: ##STR3## Third, selective reduction may take place, in accordance with the present invention. In this reaction the halogen is replaced by hydrogen, as in the examples of this application.
In order for the reduction reaction to work, the ether must not undergo a hydrolysis or nucleophilic displacement reaction or dehydrohalogenation reaction, which is faster than the reduction. In addition, any ether formed by the reduction reaction must not undergo further reactions, especially dehydrohalogenation.
In order for selective reduction to take place, rather than hydrolysis or nucleophilic displacement or dehydrohalogenation, certain conditions must be met. The reactions of the halogenated ethers have been little explored and have been considered highly unpredictable. The present invention is remarkable in that only certain halogenated ethers can be selectively reduced, and in that the reduction is selective.